Differences in blood levels of neuroligin-derived peptides in a cohort for early detection of Alzheimer’s disease

Abstract Alzheimer’s disease (AD) develops gradually, with significant neurodegeneration already present by the time clinical symptoms emerge. Since synapses are affected early in the disease, synaptic proteins are being investigated as potential markers of the prodromal stage. Using data and plasma samples provided by the Consortium for the early identification of Alzheimer’s disease—Quebec (CIMA-Q), we analyzed plasma levels of neuroligin (NLGN)-derived peptides in cognitively normal (CN) individuals and cognitively impaired (CI) individuals, including those with amnestic mild cognitive impairment (aMCI) and early-stage Alzheimer’s disease (AD). Plasma levels of NLGN-derived peptides were assessed by quantifying tryptic peptides using liquid chromatography coupled with tandem mass spectrometry. Our findings show that levels of specific NLGN peptides were significantly elevated in CI compared to CN individuals. Receiver operating characteristic (ROC) curve analysis revealed that some NLGN peptides could distinguish CI individuals. Furthermore, analysis based on Mini-Mental State Examination (MMSE) scores revealed that specific plasma phosphorylated tau peptides were significantly and positively correlated with selected NLGN-derived peptides in more advanced stages of cognitive decline. These results support further investigation into synaptic NLGN-derived peptides in the blood as promising tools for monitoring the earliest stages of AD.